Fig. 2: A library of ATSP-7041 analogs uncovers design trends.
From: Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists
For clarity, the N-terminal azido-lysine and beta-alanine residues are not shown in the helical wheel diagrams. Compounds coloured in blue represent acidic residues, those in red represent basic residues, and those in black represent apolar residues. Compounds were tested in duplicate. a Aside from the critical contact residues (F3, W7, & Cba10), substitutions with a variety of amino acids tend to maintain high affinity binding ( < 250 nM). b Single substitutions to charged residues (K, R, hR (homo-Arg), H, E) at non-binding positions, tend to result in decreased cellular activity while substitutions to other types of residues had varying affects.
